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- Title
T cells and eosinophils in bronchial smooth muscle cell death in asthma.
- Authors
Solarewicz-Madejek, K.; Basinski, T. M.; Crameri, R.; Akdis, M.; Akkaya, A.; Blaser, K.; Rabe, K. F.; Akdis, C. A.; Jutel, M.
- Abstract
Background Bronchial smooth muscle cells (SMC) proliferate, express adhesion molecules, secrete cytokines and thus efficiently contribute to the pathogenesis of asthma. Objective The aim of the study was to investigate whether, and by which mechanism, T cells and eosinophils can cause death of airway SMC. Methods The T cell- and eosinophil-induced cell death was analysed in primary human bronchial SMC cultures as well as in bronchial biopsy specimens from non-asthmatic and asthmatic individuals. Results Bronchial SMC death showed characteristic morphological features of apoptosis in 3–6 days cultures with inflammatory cytokines (IFN-γ, TNF-α), soluble death ligands [sFasL, TNF-related apoptosis-inducing ligand (TRAIL)] and activated T-helper type 1 (Th1) and Th2 cell supernatants. The recombinant eosinophil cationic protein induced SMC necrosis within 1 h. Resting SMC expressed the death receptors TNFR1, TNFR2, Fas, TRAILR1, TRAILR2 and membrane FasL as a death-inducing ligand. IFN-γ and TNF-α up-regulated TNFR1, TNFR2, Fas and membrane FasL on SMC. TNF-α up-regulated TRAILR1 and TRAILR2; sFasL up-regulated TNFR2. The intracellular caspase-3 activation in SMC was significantly increased by IFN-γ, sFasL, TRAIL, Th1 and Th2 cell supernatants. Increased expression of TRAIL in asthmatics, but not in non-asthmatic individuals was demonstrated in situ. The apoptosis receptors TRAILR1 and TRAILR2 were expressed in SMC and epithelial cells both in healthy and asthmatic biopsies. Prominent apoptosis of SMC was observed in fatal asthma, but not intermittent asthma biopses. Conclusion The demonstration of bronchial SMC death both by apoptosis and necrosis indicates the essential role of T cells and eosinophils in the bronchial tissue injury particularly in the severe asthma.
- Subjects
T cells; EOSINOPHILS; CELL death; ASTHMA; MUSCLE cells; APOPTOSIS
- Publication
Clinical & Experimental Allergy, 2009, Vol 39, Issue 6, p845
- ISSN
0954-7894
- Publication type
Article
- DOI
10.1111/j.1365-2222.2009.03244.x